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RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.
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Objective To investigate the effect of blue light on the dioptric development of the eyes of lens-induced myopia(LIM)guinea pigs.Methods Three-week-old trichromatic guinea pigs were randomly divided into three groups:control group,white light LIM(WL)group,and blue light LIM(BL)group(420 nm LED light,with an illuminance of 700 lx);guinea pigs in the latter two groups wore-10.00 D lenses in their right eyes to induce myopia.All guinea pigs under-went a 12 h light/12 h dark treatment cycle.Before and 2,4 weeks after the intervention,the diopter,axial length,retinal thickness and choroidal thickness were measured in all groups.After 4 weeks of intervention,the corneal fluorescent stai-ning and retinal Hematoxylin and Eosin(HE)staining were conducted.Results Compared with the control group,from week 0 to week 2 of the intervention(changes in weeks 0-2),the eyes in the WL group drifted(-2.22±1.28)D towards myopia,the axial length lengthened by(0.40±0.05)mm,and the retinal and choroidal thicknesses reduced by(-7.42± 7.04)μm and(-6.29±4.66)μm,respectively;compared with the WL group,in the BL group,the eyes drifted toward hyperopia by(0.48±1.16)D,the axial length increased by(0.20±0.10)mm,and retinal and choroidal thicknesses in-creased by(1.36±7.46)μm and(8.05±8.08)μm,respectively(all P＜0.05).From week 2 to week 4(changes in weeks 2-4),compared with the control group,the diopter in the WL and BL groups progressed towards myopia,with changes of(-4.64±0.50)D and(-2.11±2.02)D,respectively(both P＜0.05);the axial length lengthened,and reti-nal and choroidal thicknesses reduced in the WL group,with changes of(0.44±0.06)mm,(-7.35±5.87)μm and(-4.84±2.61)μm,while the choroidal thickness and the retinal thickness decreased in the BL group,with changes of(-0.33±5.95)μm and(-4.78±4.96)μm,respectively.Observations of corneal fluorescence staining and retinal HE staining indicated that prolonged blue light exposure could lead to damage to corneal and retinal cells.Conclusion Blue light may influence the development of myopia through choroid-related mechanisms,but its inhibitory effect is not positive-ly correlated with time.Prolonged exposure to blue light can damage the cornea and retina,thereby reducing the inhibitory effect.
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The complex function of the brain depends on the interaction of its intrinsic neurons and neural network systems,in which glutamatergic projection neurons and GABAergic inhibitory interneurons play an important role.There is a critical period in the postnatal development of the visual system when it is susceptible to the external environment,which may affect visual plasticity.Changes in the visual environment can lead to adaptive adjustment in neural connections and synaptic structures among visual cortexes,and the perineural network in the extracellular matrix has been proven to play an essential role in this process.The parvalbumin-positive inhibitory interneurons(PV+INs)contained in the perineural net-works are also involved in regulating plasticity during the critical period of visual development.PV+INs are a kind of inter-neurons that express the parvalbumin found in various parts of the brain.Recent studies have demonstrated that specific modulation of these neurons not only reveals some potential therapeutic mechanisms for disorders such as amblyopia,de-pression and autism but also provides a more precise treatment for these diseases.In this paper,various regulatory factors of PV+INs from their origin to the end of the critical period of visual development and their involvement in visual develop-mental plasticity were reviewed,with the aim of providing some guidance for basic research on visual cortical plasticity.
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AIM: To observe the characteristics of microperimetry in patients with glaucoma, and investigate the correlation between microperimetry and best corrected visual acuity(BCVA), standard automatic perimetry and optical coherence tomography(OCT)index.METHODS: This case-control study included 45 patients(76 eyes)with glaucoma(glaucoma group), among which 15 patients(25 eyes)with primary open-angle glaucoma and 30 patients(51 eyes)with chronic angle-closure glaucoma, and 40 healthy individuals(76 eyes)were included in the control group. MAIA microperimetry, Humphrey perimetry, and BCVA tests were performed in all examined eyes. Correlation analysis was performed using the structural indices measured by OCT.RESULTS: The mean sensitivity(MS)in macular area measured by microperimetry and the ganglion cell complex(GCC)and retinal nerve fiber layer(RNFL)thickness measured by OCT were decreased in glaucoma patients when compared to the control group. Additionally, the mean defect(MD)measured by Humphrey perimetry(10-2 visual field test), focal loss volume(FLV), global loss volume(GLV)measured by OCT, and 63% bivariate contour ellipse area(BCEA )measured by MAIA microperimetry were higher than those of the control group. The MS was negatively correlated with MD, FLV, GLV and BCVA(LogMAR)in the glaucoma group(rs=-0.839, -0.665, -0.530, and -0.424, all P<0.01). In contrast, MS was positively correlated with GCC and RNFL in the glaucoma group(rs=0.437, 0.500, all P<0.01). MAIA microperimetry had a shorter detection time. Receiver operating characteristic(ROC)curve analysis showed that MAIA microperimetry had moderate accuracy for the diagnosis of glaucoma.CONCLUSIONS: MAIA microperimetry has high sensitivity and can detect retinal sensitivity reduction in areas of structural damage tested by OCT. The microperimetry values were correlated with BCVA, standard automatic perimetry parameters, and OCT parameters. MAIA microperimetry combined with OCT will increase the early diagnosis rate of glaucoma.
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The impairment of optic disc and retinal function caused by intraocular pressure is one of the main causes of irreversible visual impairment.In addition to the effects of intraocular pressure, studies have found that ocular adduction and horizontal abduction movements affect the optic disc and surrounding retinal tissue, which result in mechanical pressure and traction having influences on tissue and this change is related to the rotation angle, speed, and age, etc.Studies have found that horizontal eye movements can cause changes in the nasal and temporal sides of the optic disc, as well as the surrounding retinal and choroidal structures, and these changes vary among different age groups.This paper reviewed the current research on the effects of horizontal eye movements on the morphology of the optic nerve and retina, in order to provide some useful clues for the treatment of relevant diseases in clinical practice.
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This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.
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Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.
الموضوعات
Animals , Mice , Glucosides , Mice, Inbred BALB C , Molecular Docking Simulation , Monoterpenes , Paeonia , Plant Rootsالملخص
The pathogenesis of hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC） is complicated with the crosstalk of multiple factors and the multi-step processes. The main mechanisms underlying the HBV-induced HCC include:①integration of HBV DNA into the host hepatocyte genome to alter gene function at the insertion site，resulting in host genome instability and expression of carcinogenic truncated proteins;②HBV gene mutations at S，C，and X coding regions in the genome;③HBV X gene-encoded HBx protein activates proto-oncogenes and inhibits tumor suppressor genes，leading to the HCC occurrence. In this article，the recent research progress on the molecular mechanism of HBV-induced HCC is comprehensively reviewed，so as to provide insights into the prevention，early prediction and postoperative adjuvant therapy of HCC.
الموضوعات
Humans , Carcinoma, Hepatocellular , Hepatitis B/complications , Hepatitis B virus/genetics , Hepatocytes , Liver Neoplasmsالملخص
BACKGROUND@#Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development.@*METHODS@#Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors.@*RESULTS@#A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206).@*CONCLUSIONS@#IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
الموضوعات
Humans , Albumins/analysis , Antiviral Agents/administration & dosage , Betacoronavirus , C-Reactive Protein/analysis , COVID-19 , Case-Control Studies , China , Coronavirus Infections/drug therapy , Glucocorticoids/pharmacology , Hospitalization , Interferon alpha-2/administration & dosage , Nasal Sprays , Pandemics , Pneumonia, Viral/drug therapy , Propensity Score , Retrospective Studies , SARS-CoV-2 , Sodium/blood , Virus Shedding/drug effects , COVID-19 Drug Treatmentالملخص
Objective:To investigate the value of clinical monitoring of regional cerebral oxygen saturation (SctO2) for severe traumatic brain injury (sTBI). Methods:From December, 2017 to January, 2019, 33 patients with sTBI within 24 hours were monitored SctO2, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) with near-infrared spectroscopyonce per six hours for seven days. They were assessed with Glasgow Coma Score (GCS) at admission and Glasgow Outcome Score (GOS) six months after injury. Results:SctO2 was the lowest on the third day of monitoring, and then increased gradually. SctO2 negatevely correlated with ICP (r < -0.857, P < 0.001), and positively correlated with GCS, CPP and GOS (r > 0.697, P < 0.05). Conclusion:SctO2 monitoring is valuable after sTBI to identify the secondary injuries and severity of injuries, and predict the outcome partly.
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Background: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. Methods: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. Results: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). Conclusions: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
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BACKGROUND@#A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure.@*METHODS@#We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan.@*RESULTS@#Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups.@*CONCLUSIONS@#From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.
الموضوعات
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Aspartate Aminotransferases , Blood , Betacoronavirus , Case-Control Studies , China , Epidemiology , Coronavirus Infections , Epidemiology , Therapeutics , L-Lactate Dehydrogenase , Blood , Pandemics , Pneumonia, Viral , Epidemiology , Therapeutics , Retrospective Studiesالملخص
Objective By analyzing the pancreas islet function characteristics of initial diagnosed type 2 diabetes patients to provide guidance of selecting hypoglycemic drugs to lower the risk occurrence of main cardiovascular adverse event(MACE)in patients with coronary arterial atherosclerotic cardiac disease (coronary disease) combined with diabetes mellitus. Methods The clinical data of 769 initial diagnosed type 2 diabetic patients admitted to Tianjin Hongqiao Hospital from January 2013 to July 2018 were retrospectively analyzed. The patients were divided into a synchronous group (542 patients) and a non-synchronous group (227 patients) according to whether the insulin and C-peptide secretion peak times were synchronized or not. The pancreas islet function characteristics of the two groups were analyzed, the differences in the levels of total cholesterol (TC), triacylglycero(TG), glycosylated hemoglobin (HbA1c),oral glucose tolerance test (OGTT), serum insulin release (INS), C-peptide detection index, peak times of insulin and C-peptide, insulin resistance index of steady state model (HOMA-IR), steady-state insulin secretion index (HOMA-β) , and quantitative insulin sensitivity test index (QUICKI) were compared between the two groups; Logistic binary regression analysis was used to screen out the risk factors that could be related to the impact of whether the peak value times of insulin and C peptide being synchronous or not in initial diagnosed type 2 diabetic patients. Results The TC in the synchronous group was significantly higher than that in the non-synchronous group (mmol/L: 4.96±1.20 vs. 4.78±1.06), and the HbA1c was obviously lower than that in non-synchronous group (0.077 5±0.016 6 vs. 0.082 7±0.018 6), the differences being statistically significant (all P<0.05). The blood glucose, insulin levels of the two groups gradually increased with time and peaked at 120 minutes, and then went down, and the blood glucose level of the synchronous group was significantly lower than that of the non-synchronous group (mmol/L:15.52±3.39 vs. 16.18±3.97), while the levels of insulin in the synchronous group were significantly higher than those in the non-synchronous group (mU/L: 92.19±78.34 vs. 55.99±49.86, both P<0.05). After 120 minutes, the level of C-peptide in synchronous group was significantly higher than that in non-synchronous group (μg/L: 2.34±0.52 vs. 2.16±0.59), and lasted to 180 minutes (μg/L: 9.96±4.71 vs. 8.99±4.33). The peak time of insulin in the synchronous group was significantly delayed than that in non-synchronized group (minutes: 125.54±28.02 vs. 93.30±40.91), but the C-peptide secretion peak time was earlier (minutes: 125.54±28.07 vs. 145.11±32.61), the differences being statistically significant (all P<0.05). There were no significant differences in HOMA-IR, QUICKI between the two groups [HOMA-IR:(4.31±3.35)% vs. (4.15±3.46)%, QUICKI: 0.32±0.04 vs. 0.33±0.05, both P>0.05], and the HOMA-β of synchronous group was significantly higher than that in the non-synchronous group [(88.64±67.53)% vs. (76.59±69.41)%, P<0.05], ISI in synchronous group was significantly lower than that in non-synchronous group (3.98±0.66 vs. 4.14±0.74, P<0.05). Logistic regression analysis showed that the factors of affecting the synchronization of insulin and C-peptide release were insulin peak time and C-peptide peak time [insulin peak time: odds ratio (OR) = 1.077, 95% confidence interval (95% CI)=1.066-1.088; peak time of C peptide: OR=0.928, 95%CI=0.918-0.938]. Conclusion The degree of insulin resistance in synchronous group is higher than that in non-synchronous group; and the secretion function of pancreas islet beta cells in non-synchronous group is lower than that in synchronous group; the more stronger insulin resistance is, the more synchronous the release curve of insulin and C-peptide is.
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OBJECTIVE@#To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD).@*METHODS@#A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD.@*RESULTS@#There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P<0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P<0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P<0.05).@*CONCLUSIONS@#The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.
الموضوعات
Child , Humans , Autism Spectrum Disorder , Bacteria , Feces , Gastrointestinal Microbiome , RNA, Ribosomal, 16Sالملخص
To explore the effect of total extract of Chrysanthemum morifolium on lipopolysaccharide (LPS)-induced acute lung injury in mice, we studied the effects of three caffeoyl quinic acids isolated from Chrysanthemum morifolium on vascular endothelial cell injury and their mechanisms of action. All animal experiments were carried out strictly in accordance with the National Animal Welfare Ethics and Protection Regulations. A mouse model of acute lung injury was established by intranasal instillation of LPS. After 6 days of oral administration of chrysanthemum extract, the lung wet weight/dry weight ratio, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured in mouse bronchoalveolar lavage fluid. Human umbilical vein endothelial cells (HUVEC) were serum starved for 12 h and treated with 2.5 μg·mL-1 LPS for 24 h to establish the in vitro model of vascular endothelial cell injury. After 24 h of treatment of caffeoyl quinic acids from Chrysanthemum morifolium, the levels of TNF-α, IL-6, IL-1β, vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) were measured by ELISA in the cell culture supernatant, the malondialdehyde (MDA) level was detected by TBA method, the superoxide dismutase (SOD) level was determined by hydroxylamine method, and the nitric oxide (NO) level was assayed by a one-step method. The levels of p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2, p-JNK, JNK, p-P38 and P38 of mitogen-activated protein kinase (MAPK) signaling pathway were detected by Western blot. The total extract of Chrysanthemum morifolium can significantly reduce the wet weight/dry weight ratio of lung in mice and the levels of TNF-α, IL-6 and IL-1β in alveolar lavage fluid. The caffeoyl quinic acids from Chrysanthemum morifolium significantly increased the levels of SOD and NO, decreased the levels of TNF-α, IL-6, IL-1β, VCAM-1, ET-1 and MDA, and significantly reduced the levels of p-MEK1/2, p-ERK1/2. In conclusion, total extracts of Chrysanthemum morifolium exhibit certain protective effect on mice with acute lung injury, and three caffeoyl quinic acids from Chrysanthemum morifolium may improve LPS-induced vascular endothelial cell injury by inhibiting inflammatory cytokines and oxidative stress, and regulating inter-cellular adhesion molecule and vasomotor factors through ERK/MAPK signaling pathway.
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Objective To detect the level of serum syndecan-1 in patients with oral tongue squamous cell carcinoma (OTSCC),and to investigate the effect of serum syndecan-1 in OTSCC diagnosis and disease progression assessment.Methods The serums of a total of 65 OTSCC patients (OTSCC group) and 74 healthy subjects (control group) were collected from March 2015 to June 2017 in the Fourth Hospital of Xi'an.Enzyme linked immunosorbent assay was used to detect the level of serum syndecan-1.Receiver operating characteristic (ROC) curve was conducted to evaluate the diagnostic value of serum syndecan-1 in OTSCC and its disease progression.Results The level of serum syndecan-1 in OTSCC group was significantly lower than that in the control group [(91.87 ± 33.18) ng/ml vs.(162.32 ± 51.16) ng/ml,t =1.977,P =0.002].The serum syndecan-1 levels of different TNM stage (F =3.536,P =0.025),tumor invasive depth (F =1.254,P =0.039) and lymph node metastasis (t =2.420,P =0.018) in OTSCC group had statistically significances.ROC curve analysis showed that 95.54 ng/ml serum syndecan-1 [area under the curve (AUC) =0.944,P ＜ 0.001,95％ CI:0.915-0.974] was the cut-off value of OTSCC diagnosis,and 74.54 ng/ml of lymph node metastasis in OTSCC diagnosis (AUC =0.783,P ＜ 0.001,95％ CI:0.697-0.867).Conclusion Serum syndecan-1 level is markedly decreased in patients with OTSCC,and is valuable to diagnose OTSCC or its lymph node metastasis,which is worthy of clinical application.
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Objective To investigate the therapeutic benefits of tonsillectomy combined with suspension sutures on Friedman stageⅠ obstructive sleep apnea-hypopnea syndrome(OSAHS). Methods Forty-four pa-tients with Friedman stageⅠOSAHS diagnosed and treated from January 2014 to December 2016 were divided into experimental group with 23 patients receiving tonsillectomy combined with suspension sutures and the control group with 21 receiving modified uvulopalatopharyngoplasty. Apnea-hypopnea index(AHI),lowest oxygen saturation (LSaO2)and Epworth Sleepiness Scale(ESS)score were compared between the groups pre- or post-operatively. Results Surgical success rate did not differ significantly between 2 groups(82.6% in the experimental group and 80.9% in the control group). Inner-group comparison indicated that AHI and ESS were significantly lower(P <0.001)while LSaO2was significantly higher after the operation(P < 0.001). There were,however,no significant differences in pre-or post-operative BMI,AHI,ESS or LSaO2between the experimental and control group(all P≥0.05).Conclusion Tonsillectomy combined with suspension sutures is effective for Friedman stageⅠOSAHS.
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Promyelocytic leukemia (PML) protein, a tumor suppressor, plays an important role in patients with acute promyelocytic leukemia (APL) receiving arsenic trioxide (AsO) therapy. APL is a M3 subtype of acute myeloid leukemia (AML), which is characterized by expression of PML-RARα (P/R) fusion protein, leading to the oncogenesis. AsO is currently used as the first-line drug for patients with APL, and the mechanism may be:AsO directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Gene mutations may lead to relapse and drug resistance after AsO treatment. In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with AsO; and explain how PML protein mutations could cause resistance to AsO therapy.
الموضوعات
Humans , Antineoplastic Agents , Therapeutic Uses , Arsenic Trioxide , Therapeutic Uses , Drug Resistance, Neoplasm , Genetics , Leukemia, Promyelocytic, Acute , Drug Therapy , Mutation , Oncogene Proteins, Fusion , Metabolism , Promyelocytic Leukemia Protein , Chemistry , Genetics , Metabolismالملخص
Objective To investigate the correlation between cerebral infarction and homocysteine (Hcy) level and atherosclerosis index (ASI) , and to provide reference for prevention and treatment of cerebral infarction. Methods 2525 patients hospitalized with cerebral infarction and 8151 healthy subjects were included in the study, the blood serum homocysteine and blood lipid levels were detected by enzymatic cycling and enzymatic method, and the ASI was calculated according to the results of blood lipid test. The risk factors of cerebral infarction were analyzed by logistic regression analysis model. Results The Physical examination Health Group male 4952, female 3199, average (45.65±10.77) years old, in the cerebral infarction Group male 1590 cases, female 935, average (65.47±12.16) years old. A total of 360 patients with high homocysteine were detected in the Health examination group, the detection rate was 4.42%, the cerebral infarction group detected 268 patients with high homocysteine, the detection rate was 10.61%, and the difference was statistically significant (P<0.01) . Logistic regression analysis showed that age (OR=1.147, 95%CI: 1.140~1.154), homocysteine (OR=1.022, 95% CI: 1.010 ~1.035) and total cholesterol (OR=2.815, 95% CI: 2.603 ~3.045) level, ASI (OR=1.914, 95%CI: 1.794~2.042) are the risk factors of cerebral infarction, women (OR=0.694, 95%CI: 0.606~0.697) are the protective factors for the occurrence of cerebral infarction. Conclusion Serum homocysteine and total cholesterol levels, ASI elevated can increase the risk of cerebral infarction, regular detection of serum homocysteine and lipid levels can help early detection and prevention of cerebral infarction.
الملخص
<p><b>BACKGROUND</b>The 9-hole peg test (9-HPT) and 10-meter walk test (10-MWT) are commonly used to test finger motor function and walking ability. The aim of this present study was to investigate the efficacy of these tests for evaluating functional loss in Chinese Charcot-Marie-Tooth (CMT) disease.</p><p><b>METHODS</b>Thirty-four Chinese CMT patients (CMT group) from August 2015 to December 2016 were evaluated with 9-HPT, 10-MWT, CMT disease examination score, overall neuropathy limitation scale (ONLS), functional disability score, and Berg Balance Scale (BBS). Thirty-five age- and gender-matched healthy controls (control group) were also included in the study. Student's nonpaired or paired t-test were performed to compare data between two independent or related groups, respectively. The Pearson test was used to examine the correlations between recorded parameters.</p><p><b>RESULTS</b>The mean 9-HPT completion time in the dominant hand of CMT patients was significantly slower than that in the healthy controls (29.60 ± 11.89 s vs. 19.58 ± 3.45 s; t = -4.728, P < 0.001). Women with CMT completed the 9-HPT significantly faster than men with CMT (dominant hand: 24.74 ± 7.93 s vs. 33.01 ± 13.14 s, t = 2.097, P = 0.044). The gait speed of the average self-selected velocity and the average fast-velocity assessed using 10-MWT for CMT patients were significantly slower than those in the control group (1.03 ± 0.18 m/s vs. 1.44 ± 0.17 m/s, t = 9.333, P < 0.001; 1.31 ± 0.30 m/s vs. 1.91 ± 0.25 m/s, t = 8.853, P < 0.001, respectively). There was no difference in gait speed between men and women. Both 9-HPT and 10-MWT were significantly correlated with the ONLS, functional disability score, and BBS (P < 0.05 for all).</p><p><b>CONCLUSION</b>The 9-HPT and 10-MWT might be useful for functional assessment in Chinese patients with CMT.</p>